[en] The viral Tax oncoprotein is a critical contributor to the development of adult T-cell leu- kemia/lymphoma, an aggressive malignant proliferation of T lymphocytes. Tax contains a PDZ domain-binding motif (PBM) that favors the interaction with several cellular PDZ proteins. Here, we compare the in vivo involvement of the Tax PBM in humanized mice infected with either a full-length provirus or a Tax PBM-deleted provirus. We observe that the establishment of the sustained lymphoproliferation in the peripheral blood of infected mice is dependent on the Tax PBM. Furthermore, binding of the Tax PBM to the PDZ Scribble protein correlated with perturbations of cytoskeletal organization and cell polarity. In addition, genome-wide transcriptomic analyses strongly suggest that the asso- ciation of Tax PBM with cellular PDZ proteins results in the expression of several genes involved in proliferation, apoptosis and cytoskeletal organization. Collectively, these results indicate that the Tax PBM is an auxiliary motif that contributes to the growth of HTLV-1 infected T-cells. As a consequence, targeting the PBM/PDZ nodes using small peptides may have the potential to antagonize the Tax-induced lymphoproliferation, offering a novel strategy for the treatment of this disease.
Disciplines :
Microbiology
Author, co-author :
Pérès, Eléonore; Ecole Normale Supérieure - Lyon > Laboratory of Biology and Modeling of the Cell
Blin, Juliana; Ecole Normale Supérieure - Lyon > International Center for Infectiology Research
P. Ricci, Emiliano; Ecole Normale Supérieure - Lyon > International Center for Infectiology Research
Artesi, Maria ; Université de Liège - ULiège > GIGA-Research
Hahaut, Vincent ; Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > GIGA-R : Génomique animale
Van den Broeke, Anne; Institut Jules Bordet > Laboratoire d'hématologie expérimentale
Corbin, Antoine; Ecole Normale Supérieure - Lyon > International Center for Infectiology Research
Gazzolo, Louis; Ecole Normale Supérieure - Lyon > Laboratory of Biology and Modeling of the Cell
Ratner, Lee; University of Washington - UW > Division of Oncology
Jalinot, Pierre; Ecole Normale Supérieure - Lyon > Laboratory of Biology and Modeling of the Cell
Duc Dodon, Madeleine; Ecole Normale Supérieure - Lyon > Laboratory of Biology and Modeling of the Cell
Language :
English
Title :
PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice
Publication date :
22 March 2018
Journal title :
PLoS Pathogens
ISSN :
1553-7366
eISSN :
1553-7374
Publisher :
Public Library of Science, United States - California
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